This invention relates to the use of protein S and/or variants thereof as neuroprotective agents for treating brain disorders and other pathological conditions. The ability of protein S and variants thereof to act as cell survival factors on cells of the nervous systems are demonstrated.
Benzakour and Kanthou (Blood 95:2008-2014, 2000) showed that protein S is produced by smooth muscle cells derived from abdominal arteries. They suggested that protein S may be an important autocrine factor in the pathophysiology of the vasculature by acting as a mitogen for these cells. In more recent work, they induced apoptosis of abdominal vessel, smooth muscle cells using sodium nitroprusside or hydrogen peroxide. Pre-treatment with protein S reduced apoptosis and cell death (Kanthou & Benzakour in Angio-genesis: From the Molecular to Integrative Pharmacology, pp. 155-166, 2000).
These studies did not address the role of protein S in the nervous system or, more specifically, its effects on brain endothelial cells.
The present invention addresses the need for neuroprotective compositions and methods for their use to treat diseases associated with a variety of types of nervous system damage, thrombosis, and inflammation. Because injury usually occurs after a triggering event, treatment may be initiated after such an event.
Therefore, it is an objective of the invention to show how to use protein S and variants thereof as neuroprotective agents. A long-felt need for new therapeutic and prophylactic compositions is addressed thereby. Also provided are compositions that have been formulated to deliver protein S or variants thereof to the central nervous system and processes for using and making the aforementioned products. Further objectives and advantages of the invention are described below.